POS0113 LONG-TERM REMISSIONS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR AUTOIMMUNE DISEASES – A 25 YEARS SINGLE CENTER EXPERIENCE
Authors: T. Alexander, R. Biesen, G. R. Burmester, A. Radbruch, R. Arnold, F. Hiepe
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The introduction of novel targeted biologic therapies has dramatically improved the treatment landscape for autoimmune diseases (AD). However, although providing more specificity, such therapies routinely depend on continuous or repeated administration, with a cumulative risk of long-term side effects, and are not curative. In contrast, immunoablation followed by hematopoietic stem cell transplantation (HSCT) has emerged as a promising on-off therapy over the past decades, to provide long-term remissions even in patients with severe courses of their disease, through the restoration of immunologic self-tolerance [1]. <h3>Objectives</h3> Here, we summarize the outcomes of AD patients receiving HSCT at the Charité – University Medicine between February 1998 and October 2015. <h3>Methods</h3> In this retrospective study, the clinical outcome of 22 patients was analyzed, who received a CD34<sup>+</sup>-selected autologous HSCT after immunoablation with 200mg/kg cyclophosphamide and 90mg/kg rabbit antithymocyte globulin (ATG) for autoimmune diseases. Indication for transplant were systemic lupus erythematosus (SLE, n=10), systemic sclerosis (SSc, n=4), vasculitis (n=3), multiple sclerosis (MS, n=2), polychondritis (n=1), chronic inflammatory demyelinating polyneuropathy (CIDP, n=1) and autoimmune hemolytic anaemia (AIHA, n=1). The median age at transplant was 29 years (range 16-48), and 82% of patients were female. Multiparamter flow cytometry was applied to characterize peripheral blood lymphocytes subsets, assessment of SIGLEC-1 expression on monocytes as surrogate for type-I interferon (IFN-I) activity in SLE. <h3>Results</h3> With a median follow-up of 78 months (range 0.1-300), the overall survival was 76.4% and progression-free survival 58.2%, respectively. 3 deaths were regarded treatment related (2 infections in SLE and 1 cardiac failure in SSc). One patient had persisting disease (AIHA) and 4 relapses occurred in SLE patients at 18, 36, 81 and 83 months, respectively. Remaining patients are in stable clinical remission for up to 25 years post-transplant, despite discontinuation of immunosuppressive therapy in most cases. HSCT was associated with significant reduction or normalization of autoantibody levels and a profound reconfiguration of the adaptive immune system, the latter characterised by a re-emergence of naïve T cells with markers of recent thymic emigrants, including Foxp3<sup>+</sup> Tregs and regeneration of naïve B cells. In SLE patients, SIGLEC-1 expression on monocytes completely normalized suggesting an abrogation of type I interferon signalling in responding patients. <h3>Conclusion</h3> Our data provide the `proof-of-concept` that a chronic autoimmune system can be reset into a naïve and self-tolerant state by immunoablation and HSCT, providing a potential curative treatment option. Although initially applied as salvage therapy in severely affected patients with poor outcomes, transplantation related mortality has gradually improved over the past years, due to accumulating centre experience, better patient selection and improved supportive care. Therefore, HSCT still resembles a promising treatment option, especially in those patients with insufficient response to standard-of-care, with poor prognosis and live-threatening disease, in which the risk:benefit ratio of HSCT seems acceptable. <h3>Reference</h3> [1]Alexander T, Greco R. Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2022 Jul;57(7):1055-1062. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Tobias Alexander Grant/research support from: Amgen, Miltenyi, Janssen, Robert Biesen: None declared, Gerd Rüdiger Burmester: None declared, Andreas Radbruch: None declared, Renate Arnold: None declared, Falk Hiepe: None declared.